The proposed research will provide molecular and biological data on a novel virus group, the salivary gland hypertrophic viruses (SGHVs), which impacts insect vectors of both human and animal diseases. Presently, the SGHVs have both detrimental and beneficial impacts on disease vectors. This virus is established (asymptomatically) in all tsetse fly colonies worldwide and therefore threatens the use of sterile insect technologies (SIT) against vectors of both human African trypanosomiasis and animal nagana. Recently, the International Atomic Energy Agency (IAEA) recognized the severity of the problem by funding a five-year project to eliminate this virus from mass- rearing facilities. On the other hand, this virus rapidly sterilizes the female house fly, thus providing an opportunity to develop a biologically based birth control for managing this disease vector. SGHVs are unique; these viruses infect adults, display a high degree of host and tissue specificity, and do not impact growth and survival of the host, but they do sterilize infected adults. Furthermore, the SGHVs have evolved transmission mechanisms suited to their respective hosts. The house fly SGHV is transmitted via salivary contamination of food. The house fly, an r-strategist, exists in nature at high densities and readily picks up this virus by feeding on food previously exposed to infected flies. To date, there is no evidence of vertical or venereal transmission; survival of the house fly SGHV relies upon the continuous release of high numbers of environmentally stable, enveloped virions. Alternatively, the viviparous tsetse fly, a k-strategist, exists in nature at relatively low densities and has little or no contact with conspecifics during blood feeding. In addition to salivary glands, the tsetse fly SGHV infects male and female reproductive tissues, allowing venereal transmission from male to female and maternal transmission to progeny via infected milk glands. Specific objectives will examine the composition and pathology of house fly SGHV using a combination of molecular, biochemical, and histological methods to examine structure/function associations. In collaboration with the IAEA team, the comparative biology of this viral group will be delineated. This exploratory research will lay the foundation for utilizing the SGHVs as birth control for house flies and as vehicles to deliver paratransgenes into tsetse flies and for developing the house fly as a model system to screen antiviral therapies and to teach virus biology. The proposed research will characterize a novel virus group, the salivary gland hypertrophy viruses (SGHVs), which infect insect vectors of human and animal diseases. We expect that this exploratory research will reveal the mechanisms used by these DNA viruses to replicate and to persist in animal populations. Understanding how the SGHVs replicate in the salivary glands of tsetse flies and the common house fly and shut down their reproduction will open new, effective avenues for managing vector populations and provide the means to reduce the vector competence of insects. [unreadable] [unreadable] [unreadable] [unreadable]